[!INFO] Neurotransmitters used in the autonomic nervous system
Cholinergic autonomic neurons are
- all preganglionic neurons
- all prasympathetic postganglionic neurons
- sympathetic post ganglionic neurons which innervate sweat glands and blood vessels in some skeletal muscles (which dilate when stimulated)
- The remaining sympathetic post ganglionic neurons are noradrenergic
Is a bilateral collection of nuelcei divided into three zones surrounding the third ventricle and the mammillary bodies.

[!info] ACTH and TSH are the "hardiest" trophic hormones
Organic pituitary disease affects GH AND GONADOROPHINS >> ACTH AND TSH.
ACTH and TSH are the "hardiest" trophic hormones.
The "G" hormones are more sensitive
[!info] Hypothalamic Vs. Pituitary causes
Pituitary lesions won't reduce ADH secretion but hypothalamic lesions will reduce ADH secretion
| Hypothalamic diseases | Pituitary diseases |
|---|---|
| Mass lesions – Benign (craniopharyngiomas) and malignant tumors (metastatic from lung, breast, etc) | Mass lesions – Pituitary adenomas, other benign tumors, cysts |
| Radiation – For CNS and nasopharyngeal malignancies | Pituitary surgery |
| Infiltrative lesions – Sarcoidosis, Langerhans cell histiocytosis | Pituitary radiation |
| Infections – Tuberculous meningitis | Infiltrative lesions – Hypophysitis, hemochromatosis |
| Other – Traumatic brain injury, stroke | Infection/abscess |
| Infarction – Sheehan syndrome | |
| Apoplexy | |
| Genetic mutations | |
| Empty sella |

[[2021-Basic Sciences#Glucose regulating hormones|IGF]] <<- Action of IGF
[[Encodrinology MCQ discussion#Growth Hormone disorder diagnosis and investigation]]
| Hormone Type | Site of secretion | Mechanism of action | Receptor Sites | Effects | Transport | Pattern of secretion |
|---|---|---|---|---|---|---|
| Peptide | Somatotroph cells of Anterior pituitary | Mainly acts on the liver to stimulate IGF-1 production, Acts directly and indirectly on epiphyseal bone | cell membrane receptor (esp. on hepatocytes). Receptor defects cause Laron dwarfism | Pulsatile (10 pulses per day, 90 minutes each -easy to miss in a spot sample) | ||
Stimulation: GHRH, Ghrelin
Inhibition : Somatostatin
Pattern of secretion:
GH secretion peaks in early puberty
Then gradually decreases.
GH activation is mediated by many signalling pathways including the JAK2-STAT pathway.
[!TIP] IGF Vs. GH Vs. Insulin
Despite GH having anti-insulin effects, IGF-1 has insulin like activity
#2020BSQ-NOV/Q10
[!Tip] Mnemonic: GH affects all macromolecules - makes things grow
- Lipids -> increase lipolysis
- Proteins -> Increased protein synthesis
- Glucose -> Promotes insulin resistance
- Electrolytes -> Phosphate, salt and water retention
- Bone -> Epiphyseal bone growth
- So body fat content is reduced, lean body mass increases along with metabolic rate.
Other metabolic actions:
Positive nitrogen and phosphorous balance.
Metabolic rate is increased, serum cholesterol is reduced.
Na and K+ retention. (not adrenal gland mediated)
Rise in plasma phosphoros, positive nitrogen balance (but lower serum amino acid levels)
Decrease in blood urea nitrogen.
Apparently, there's an increase in urine ammonia excretions despite a positive nitrogen balance. Source and Source
In adults, causes are the same as causes of [[Hormone Physiology#Hypopituitarism|hypopituitarism]].
In children, GH deficiency can be caused by various inherited causes as well. (Acquired causes are same as in adults)
Commonest cause in adults: somatotroph adenoma
Commonest causes in children: Early childhood GH excess is usually due to GHRH excess. (i.e usually not a tumour). They will present with gigantism (or tall stature)
Causes of Increased GH presenting as gigantism (i.e ↑ GH before epiphyseal fusion)
+ Most commonly due to isolated GH excess
+ Could also be due to
+ McCune-albright syndrome - diagnosed in young adults
+ Carney complex - presents in middle aged people
+ MEN 1 and MEN 4 (4th to 5th decates of life)
+ Neurofibromatosis
+ Famlilial isolated pituitar adenomas - autosomal dominant #autosomalDominant
[[Encodrinology MCQ discussion#Growth Hormone disorder diagnosis and investigation|Diagnosis and Investigation of GH disorders]]
As commonest cause is somatotroph adenoma:
acreomegaly is associated with symptoms caused by pressure effect of adenoma:
[!Info] Hypercalcemia is MUCH more common than hypocalcemia
Usually due to primary hyperparathyroidism; occurs in older females
primary hyperparathyroidism and malignancies = 90% of cases
^da9653
[!WARNING] Hypercalcaemia >>> hypocalcaemia
Hypercalcaemia is much more common than hypocalcaemia
Vitamin D = cholecalciferol.
7-dehydrocholesterol -> + sunlight -> previtamin D3 -> Vitamin D3 --> action liver -> 25-hyroxy cholecalciferol (calcidiol) -> action of kidney -> 1,25 dihydroxy cholecalciferol. (calcitriol)
Activated vitamin D (1,25 dihydroxyvitamin D) regulates gene transcription by binding to intracellular receptors.
Mechanism: dihydroxycholecalciferol binds to it's receptor and acts as a transcription regulator which increases calbindin D proteins.
This proteins increases intestinal calcium absorption.
Induction of another protein in the renal tubules increases renal calcium absorption.
- Its most important biological action is to promote enterocyte differentiation and the intestinal absorption of calcium.
- Other effects include
- a lesser stimulation of intestinal phosphate absorption
- direct suppression of parathyroid hormone (PTH) release from the parathyroid gland,
- Stimulation of osteoblast function and matrix calcification.
- permissively allowing PTH-induced osteoclast activation and bone resorption. (indirect osteoclast activation)
- Illustrative point: "in the elderly, low vitamin D and secondary hyperperparathyroidism reduced bone mineral density" - Kumar & Clark.
^83ab8b
The renal 1-alpha-hydroxylase enzyme which activates vitamin D is regulated!
The main factors are:
#2020BSQ-NOV/Q09
When calcium is high, 1,25-dihydroxycholecalciferol synthesis is reduced and inactive 24,25-dihydroxycholecalciferol is produced instead.
Activated vitamin D levels are elevated in #pregnancy
The main reason for hypocalcemia in CKD is the impaired activation of vitamin D.
Extrarenal synthesis of vitamin D occurs in granulomatous diseases such as sarcoidosis.
| type | Site | Mechanism | Receptor sites | Effects | Transport | Pattern of secretion |
|---|---|---|---|---|---|---|
| peptide | Chief cells of parathyroid gland | ↑ osteoclast bone resorption, ↑ intestinal absorption, ↑ synthesis of D3, ↑ renal rubular resorption, ↑ phosphate excretion | cell membrane |
^0f3395
Main action is to 'mobilize calcium from bone' and increased renal phosphate excretion.
PTH increases renal phosphate excretion and increases plasma calcium by:
Parathyroid hormone secretion is directly inhibited by high calcium levels.
This happens through binding of calcium to a GPCR on the parathyroid cells called CaR.
[!INFO] Familial hypo and hypercalcemia
Loss of function mutations of CaR cause chronically elevated Calium levels. (Familial hypocalciuric hypercalcemia. (i.e normal to elevated PTH)
Gain of function mutations of CaR cause familiar hypercalciuric hypocalcemia. (?supressed PTH)
Magnesium is needed for the action of PTH. Hypomagnesaemia impairs PTH release and impairs peripheral organ sensitivity to PTH.
PTH level increases with age, possibly due to declining renal function -> reduced activated Vit D level, declining oestrogen levels and / or declining calcium absorption. Source
#2021BSQ-NOV Q08
Indications for therapeutic used:
^070bf7
About half of total calcium is protein unbound. The remainder ('complexed' to citrate and phosphate and 'unbound') making up the other half is the 'filtrable' part.
Almost all the filtered calcium is reabsorbed.
| Region | Mechanism | Percentage |
|---|---|---|
| PCT | Passive | 60% |
| TAL | 15% | |
| DCT (site of regulation) | Active | 15% |
| Collecting duct | 0% |
PTH and activated vitamin D promote calcium re-absorption in all areas except the PCT. (DCT, TAL, Connecting tubules)
Source
PTH and activated vitamin D promote expression of calcium transport proteins in these regions.
Source ^84acf2
[[Encodrinology MCQ discussion#Q 10: Hypercalcemia|MCQ discussion]]
Causes are devided into
malignancy and primary hyperparathyroidism = 90% of cases.

Causes of Severe hypercalcaemia :
Physiological compensatory mechanism for hypocalcemia.
Therefore, ↑ PTH levels, but normal calcium level.
After chronic secondary hyperparathyroidism, gland becomes autonomous.
↑Ca2+ and ↑↑ Phosphate
Not very common
In hypoparathyroidism, there is increased bone minieral density. But the bone is not properly formed.
So there are increased fractures
Caused by a defect in PTH receptor
Biochemical manifestations are just like hypoparathyroidism (Low Ca2+ and high Phosphate)
BUT having HIGH PTH level
Patients have albright phenotype
Patients have albright phenotype BUT
All biochemistry is normal
[!NOTE] What is the relationship between Calcium and Phosphate?
Calcium phosphate is insoluble and Ca and PO4 can remain in solution so long as the solubility product is not exceeded.
In patients with hyperphosphataemia, there is indeed deposition of calcium phosphate. (familiar tumoural calcinosis)
So it makes sense that as a physiological mechamism, PTH increases calcium level and simultaneously decreases phosphate level. to prevent CaPO4 depositionTo illustrate this further:
"The ensuing hyperphosphatemia may induce potentially symptomatic hypocalcemia due to calcium-phosphate precipitation in the tissues." - Source: Hyperphosphatemia
Prolonged hyperphosphataemia causes hyperparathyroidism and periarticular and vascular calcification.
Common in CKD
Can cause muscle (including diaphgram) weakness. (can cause extubation / weaning failure)
Box 9.23 in K and C #TODO
Two types of bone formation
Osteoclasts arise from macrocyte / monocyte lineage.
Cytokines essential for osteoclast function:
Bone development includes
An oversupply of osteoclasts relative to the need for remodeling or an undersupply of osteoblasts relative to the need for cavity repair are the seminal pathophysiological cellular changes in the most common bone diseases, including osteoporosis
Bone deposition and resorption is influenced by both systemic and local factors.
| Systemic | Local |
|---|---|
| + PTH & calcitriol | Prostaglandin |
| GH / IGF-1 | Transforming growth factor (TGF) |
| Glucocorticoids | Bone morphogenic proteins (BMP) |
| thyroid hormones | Cytokines |
| sex hormones | (Levels of local regulators are influenced by mechanical stress, local inflammation etc.) |
More complicated than you might think:
| Decrease bone turnover | Increase bone turnover |
|---|---|
| Parathyroid hormones - Intermittent administration -> Stimulates bone formation | PTH - Continous presense --> bone resorption |
| Calcitriol (1,25 dihydroxycholecalciferol) | If Ca and PO4 are low, high levels of Calcitriol can stimulate resorption |
| Estrogens - decrease bone turn over | glucocorticoids (glucocorticoid induced osteoporosis) |
| Calcitonin - physiologically redundant, pharmacologic doses -> onyl a transient effect of reducing bone resorption | Thyroid hormones - BOTH deposition and resorption. (bone loss can occur in hyperthyroidism) |
| TGF beta adn BMP |
Fibroblast growth factors - involved in skeletal development. Receptor mutations cause achondroplasia. [[Hormone Physiology#Growth hormone|See Laron Dwarfism]]
Synthesis occurs in follicular cells
Inorganic iodine -> Oxidation -> incorporation into thyroglobulin -> converted to MIT and DIT
MIT and DIT are converted to T3 and T4. More T4 is produced than T3. --> Bound to TBG (and albumin) --> transported.
[!INFO] only unbound (FREE) thyroid hormones can act on tissues.
only unbound (FREE) thyroid hormones can act on tissues. However, the protein bound fraction is very important for buffering and storage of thyroid hormone to prevent rapid fluctuations.
T3 binds to nuclear recetpor --> Exerts effects
T4 = prohormone (mnemonic "four" rhymes with "pro")
T3 = active metabolite; synthesized from T4 in periphery.

Thyroid hormone binds to it's nuclear receptors.
There are two isoforms - TR alpha and beta, expressed in different tissues.
Receptor-T3 complexes alter gene expression.
Overall effects of T3:
#2022BSQ Q23
| System | effect |
|---|---|
| CVS | Increase cardiac ouput |
| RS | Maintains respiratory drive |
| GI | increases motility |
| Blood | Incr. 23-DPG - increased oxygen unloading |
| Muscles | Increase speed of muscle contraction |
| Carbs | Increase gluconeogen, glycolysis, sugar absorption |
| lipid | Lipolysis + increased cholesterol turnover |
| Sympathetic NS | Increases expression of beta adrenergic receptors and in heart decreases alpha receptors |
There is a negative log-linear relationship between serum free T4 and TSH concentrations [1]. This means that very small changes in serum free T4 concentrations induce very large reciprocal changes in serum TSH concentrations. As a result, thyroid function is best assessed by measuring serum TSH, assuming steady-state conditions and the absence of pituitary or hypothalamic disease
Low TSH usually means hyperthyroidism except in
High TSH + High fT4 = TSHOma (rare) or Thyroid hormone resistance.
For this situation, administration of TRH (TRH test) will stimulate further TSH releast only in thyroid hormone resistance (TSHOma is autonomic and not controlled by TRH)
Thyroid peroxidase – TPO catalyzes the iodination of tyrosine residues of Tg to form monoiodotyrosine and diiodotyrosine. Nearly all patients with Hashimoto's thyroiditis have high serum concentrations of TPO antibodies.
Also found in 80% of Grave's disease patients.

#2021BSQ-NOV Q32
[!INFO] Is an autoimmume, T cell infiltrative disease.
Common cause of hyperthyroidism
Commoner in women - 30 - 60 years.
Autoimmunity -> TSH-Receptor antibodies (thyrotropin receptor or TRAb) stimulate thyroid gland to make thyroid hormones. -> diffuse, non tender, goiter. (MCQ Point: TSH receptor inhibiting antibodies are also formed)
Histology: Diffuse, hyperplasia and hypertrophy; follicular cells become tall and columnar with crowding and formation of papillae with no neovascularization. T cell infiltrates are present within thyroid.
Graves ophthalmolathy [[#^4c27cc|See below]] is a prominent feature. Occurs because of T cell infiltrations;
Disease follows a relapsing remitting course. Majority have recurrences.
Associated with other autoimmune diseases like myasthenia, vitiligo, pernicious anaemia
Patients will usually eventually become hypothyroid.
Orbitopathy and pretibial myxoedema are not related to thyroxine levels. Pretibial myxoedema is caused by deposition of glycosaminoglycans and T cell infiltration.
[!INFO] Definition of Graves ophthalmopathy:
Ophthalmopathy is characterized by inflammation of the extraocular muscles and orbital fat and connective tissue, which results in proptosis (exophthalmos), impairment of eye muscle function, and periorbital edema.(In a child with thyrotoxicosis) the presence of eye findings such as exophthalmos or ocular muscle dysfunction essentially always points to Graves disease. "Stare" and lid lag are common in children with any form of hyperthyroidism and occur due to increased sympathetic tone.
Volume of retro-orbital tissue is increased by 1) T cell infiltration, 2) Inflammatory oedema, 3) Increased extracellular matrix deposition, 4) increased adipocytes.
Graves dermopathy and ophthalmopathy may also be due to TRAb antibody reactivity with eye and skin tissue which may also express TSH receptor like protein. - UpToDate.
^4c27cc
[!INFO] Eye signs
Lid retraction: can be of the upper or lower eye lid. Definitions are varied and confusing.
Lid lag: Failure of the upper eye lid follow the globe as the gaze is moved donwards.
Source
As above, lid retraction is more suggestive of Grave's ophthalmopathy.
Others causes of hyperthyroidism: 
Symptomatic management: Propronolol for beta blockade.
Antithyroid drugs : thionamides: Carbimazole / methimazole and PTU
Methimazole is active metabolite of carbimazole; Equivalent dose of carbimazole is 40% higher.
[!TIP] C --> M: Alphabetical order
[!TIP] Mnemonic
PTU has a T
- It's good in T1 of pregnancy
- and thyroid STORM
- hepaTic Failure,
- vasculiTis
#2022BSQ Q16
#2021BSQ-NOV Q20
Both inhibit thyroid peroxidase which inhibits iodination of tyrosine residues on thyroglobulin.
#2020BSQ-NOV/Q20
| Carbimazole / methimazole | Propylthiouracil |
|---|---|
| General advantages of PTU: Achieves euthyroid state more quickly, Once daily dosing, less likely to cause failure of radioiodine therapy | Usually second choice except for T1, T storm |
| Less severe side effects. Usually first line choice | Usually second line, except T1 of pregnancy, <- preferred in T1 and thyroid storm |
| Blocks 5'-monodeiodinase, which converts peripheral T4 to T3 conversion | |
| Less frequent teratogenic effects | |
| Pruritus, rash, arthritis, urticaria, abnormal taste | Same |
| Agranulocytosis (0.1% incidence) | Same |
| Less risk of hepatic injury (?can cause cholestatis) | Fulminant hepatic failure |
| ANCA positive vasculitis |
Euthyroid status is expected in 4 - 6 weeks.
[!TIP] Pharmacokinetics of carbimazole / methimazole are generally better than PTU.
Carb/methimazole has longer half life.
High intrathyroidal concentrations, outlasting the plasma half life.
More inhibition of iodine organification.
Rash: Usually can be treated with antihistamine, stoppage of thionamide not required. Cross reactivity to different thionamide seen in 50%.
Agranulocytosis:
Thionamides have a high risk of agranulocytosis compared to other drugs that cause it.
Agranulocytosis occurs within 2-3 months of start of treatment.
If it occurs, treatment with thionamides is contraindicated.
Thyroiditis typically causes a painful goiter.
[!TIP] Mnemonic
De quervain - painful
Hasimotos's - chronic
Grand Seikos are japanese watches -> chronic ;)
| Hashimoto's | De quervain | Post partum | Drug induced | radiation | Infectious | Silent |
|---|---|---|---|---|---|---|
| chronic autoimmune - months to years | Post viral thyroiditis - days | rare, around 6 months post partum, resolves by 12 months PP | Lithium, interferons | radio-iodine therapy | rare, bacterial infection | |
| Rubbery gland | Painful, warm thyroid | |||||
| Transient hyper, then hypothyroidism | Hyper and then hypothyroidism | |||||
| risk factors: type 1 DM and previous episodes |
#2021GM-JUL/Q23
[!INFO] Biochemical changes in subacute thyroiditis
Adapted from UpToDate
- At the end of the graph, all 3 parameters return to normal levels.
- Note the transient hypothyroid phase.
- RAI uptake increase persists for some time after TSH elevation ?probably because the thyroid must restore it's store of thyroid hormones.
fibrous thyroiditis (Reidel's thyroiditis) -> fibrosis of the thyroid gland; woody, hard gland on palpation. Thyroid parenchyma becomes slowly replaced with dense fibroid tissue.
Presentation: Dyspnoea, Dysphagia, hoarseness due to involvement of extrathyroidal structure by the fibrosis.
| Image 1 | Image 2 |
|---|---|
|  |  |
Deranged Physiology
T3 : Low (peripheral conversion of T4 to T3 is reduced, therefore T4 may be increased)
TSH : Not elevated (i.e low or normal)
rT3 : elevated (inactive form of T3; Is a T3 antagonist)
Occurs in ill / critically ill patients.
It may be that TSH is physiologically lowered to prevent a catabolic state.
In general, thyroid functions should not be done in critically ill patients because results can be misleading.
Replacement of thyroxine is not helpful in sick euthyroid symdrome. Management is to treat the underlying disease process.
Levothyroxine (aka L thyroxine) is synthetic T4.
Prolactin is secreted by lactotroph cells in the anterior pituitary.
Level of secretion of prolantin due to a given stimulus proportional to background hyperplasia of lactotrophs which is driven by oestrogen.
Prolactin secretion by lactotrophs is under tonic inhibition of dopamine (which acts on D2 receptors of the lactotrophs) secreted by the tuberoinfundibular pathway, originating in the arcuate nucleus of the hypothalamus.
Hyperprolactinaemia causes amenorrhoea.
StatPearls prolactin
Lactotroph adenoma - usually very high prolactin levels.
Loss of dopaminergic inhibition
Oestrogen tends to increase prolactin levels.
Dopamine agonist = cabergoline and bromocriptine.
Cabergoline has less side effects.
Microadenoma -> Dopamine agonist
Macroadenoma -> dopamine agonist -> surgery
Increased blood glucose -> uptake of glucose into beta cells by GLUT-2. --> Converted to glucose-6-phosphate by islet specific glucokinase --> takes part in cellular respiration --> increased ATP --> closes ATP dependent pottasium channels --> depolarization --> influx of calcium --> secretion of golgi vessicles.
High serum amino acid also stimulates glucose secretion.
Dysfunction of islet specific glucokinase can cause one type of MODY.
Insulin binds to the insulin receptor -> it has insulin dependent tyrosine kinase activity.
[!INFO] Insulin helps to coordinate between different types of fuel used by the body.
Coordination of glucose and lipid metabolism by insulin
- in the fed stage, insulin secretion promotes glucose utilization AND storage of triglyceride in fat cells.
- In the fasting state, deficiency of insulin conserves glucose and mobilizes stored triglyceride.
Overall effect of insulin on lipid metabolism = Diversion of TGL from muscle to adipose tissue for storage.
The overall effect of increased triglyceride storage and decreased lipolysis is decreased flux of free fatty acids to the liver. This has indirect but potent action of reducing hepatic gluconeogenesis and hepatic glucose output.
Under hypoinsulinemic conditions, such as prolonged fasting or uncontrolled diabetes mellitus, fat mobilization is greatly accelerated, resulting in an oversupply of free fatty acids to the liver. In this situation, the liver synthesizes ketone bodies from the abundant supply of acetyl CoA, a by-product of incomplete beta-oxidation of long-chain fatty acids. => [[General medicine 5#DKA pathophysiology|Diabetic ketoacidosis]]
#2021BSQ-NOV Q07
[!TIP] Mnemonic
GLUT-2 and GLUT-4 : even numbered ones are involved in insulin mediated glucose regulation.
1 and 3 are basal, non insulin dependent transporters.
| Transporter | Site |
|---|---|
| SGLT-1 | small intestine and renal tubules |
| SGLT-2 | renal tubules |
| GLUT 1,3 | basal glucose uptake 'everywhere', GLUT-3 very abundant in brain |
| GLUT 2 | beta cell glucose sensor |
| GLUT 4 | insulin mediated glucose uptake in Sk and cardiac muscle, adipocytes |
| GLUT 5 | Fructose transporter |
There are three main types of estrogen: Source
[!INFO] Epidemiology of Cushing's syndrome and disease
Women are x3 to x8 time more likely than men to have Cushing's disease.
and x4 times more likely to have Cushing's syndrome due to adrenal tumour.Males had a three times greater incidence of the ectopic ACTH syndrome 30 years ago, but the increasing incidence of lung cancer in cigarette-smoking females has narrowed that margin
Commonest cause is iatrogenic;
All glucocorticoids suppress ACTH -> ACTH, and serum cortisol will be low in iatrogenic cushing's syndrome.
The diagnosis of Cushing syndrome is established when at least two different first-line tests are unequivocally abnormal, and physiologic hypercortisolism has been excluded
If a patients has feature of Chushing's syndrome
bedtime salivary cortisol
24 hour urinary free cortisol - Measures the total daily cortisol production without being affected by the cyclical variations in it's production.
Low dose DST
For bedtime salivary cortisol and UFC, two abnormal tests are required.
If cortisol is found to be elevated with the above preliminary tests, next step is to exclude physiologic hypercortisolism.
AKA - pseudo Cushing syndrome.
Clinically, these patients usually do not have skin or muscle manifestations of Cushing Syndrome.
Causes of pseudo-cushing syndrome (i.e causes of elevated cortisol)
Because of various nuances, the above tests must be unequivocally elevated in order to diagnose Cushing's syndrome. Mild elevations are unlikely to indicate Cushing's syndrome.
Once hypercortisolism has been identified and physiologic hypercortisolism as been excluded, the cause of hypercortisolism must be determined.
First step is determining if the cortisol hypersecretion is
ACTH dependent or ACTH independent.
This is done by measuring ACTH levels.
Because of cyclical variations, testing at two different times is recommended.
ACTH < 5pg/ML = ACTH independent hypercortisolism
ACTH > 20pg/mL = ACTH dependent hypercortisolism.
ACTH dependent Hypercortisolism
A mass > 6mm in size in the sella turcica supports a diagnosis of Cushing's disease.
10% of healthy people have masses <6mm in size.
Sampling the ACTH level from the petrosal sinus can be used if the diagnosis is uncertain.
[!INFO] Hypokalemia in Cushing's syndrome
- Hypertension and hypokalemia are particular prevalent in ectopic ACTH induced Cushing's syndrome.
- Normally, the kidney deactivates cortisol via the enzyme 11-beta-dehydrogenase isozyme 2 to inactive cortisone, thus 'protecting' it's mineralocorticoid receptors from the effects of cortisol. Source
- In ectopic ACTH mediated Cushing's syndrome, this inactivation is overwhelmed and cortisol acts on the aldosterone receptors -> producing hypokalemia.
- #2021GM-JUL/Q16 Deficiency of 11-beta-dehydrogenase occurs in "apparent mineralocorticoid excess".
^6a91b2
[!TIP] Mnemonic
Dopamine -> Norad -> adrenaline -> ?waste products
See also: figure 2 here: Source
Vivax and ovale infect reticulocytes.
- mefloquine - taken weakly; more convenient for long term travellers. ?to be started one week before departure.
[!WARNING] The vertebral arteries give rise to the PICA: the diagram above is wrong. It supplies the medulla, cerebellar vermis
AICA arises from the basillar artery.
#2023SBR-NOV/Q09
Context: 45 year old male presenting with ingestion of a poison causing cholinergic symptoms and hypertension with tachycardia.
Atropine:
Fuller's earth: A type of clay used as an adsorbent, filter or bleaching agent. Used in 'kitty litter' to remove the smell of cat urine.
Medically, used for treatment of paraquat ingestion, because [[Toxicology#Paraquat poisoning|Paraquat]] is intended to break down in soil. Source
Diplopia can be monocular - doesn't disappear when one eye is closed.
Binocular - present only when both eyes are open.
Binocular diplopia is most commonly caused by ocular misalignment or strabismus that can be detected using simple clinical tests
Acute onset of binocular diplopia is a red flag and needs to be investigated.
See Note in MD Work on "Overview of infections and treatment"
==HIGHLIGHTS== = working hypothesis ;) Could change
[!INFO] Regime: PPI with amoxicillin + clarithromycin | metronidazole
Read below to see why these drugs are used
==for some reason, penicillin won't work well against gram -ve bacteria==
Major concerns are with Streptococcus pneumoniae and Pseudomonas aeruginosa.
A beta lactam
Beta lactamase susceptible ! - Flucloxacillin is penicillinase resistant.
Amino group added to penicillin for some extra gram negative coverage.
Also has improved coverage of Listeria monocytogenes and Enterococcus sp
Effective against many gram positives:
-Strep pneumoniae
-pneumococci
-enterococci
Also some gram -ve
Oral amoxicillin (once or twice daily) has easier dosing schedule than oral penicillin - 6 to 12 hourly (Penicillin V).
Amoxicillin is now usually given as Co-amoxiclav . Clavulanic acid "restores" activity of amoxicllin against resistanct bacteria.
Extended spectrum penicillins ticarcillin and piperacillin-taz are active against pseudomonas
penicillinase resistant - DOC in serious MSSA infections.
Considered narrow spectrum.
Effective against Staph and Streptococcus pyogenes
==? Coamoxiclav and flucloxacillin are interchangeable==
Flucloxacillin and Co-Am can cause obstructive jaundice and hepatitis
. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as “slow substrates” or inhibitors of β-lactamases
Among beta lactams, carbapenems possess the broadest spectrum of activity and greatest potency against Gram-positive and Gram-negative bacteria
Carbapenems were discovered as a result of the search for beta lactamase inhibitors around 1970. (As beta lactamases were threatening the usefulness of penicillin at this time)
Thienamycin was a beta lactamase inhibitors that proved to be the parent molecule for all the Carbapenems.
Remarkably, thienamycin demonstrated potent broad-spectrum antibacterial and β-lactamase inhibitory activity including inhibitory microbiological activity against
Generally speaking, carbapenems enter Gram-negative bacteria through outer membrane proteins (OMPs), also known as porins.
Meropenem, biapenem, ertapenem, and doripenem are slightly more effective against Gram-negative organisms
(i) ertapenem has a more limited spectrum, because it is not as active as imipenem or meropenem against P. aeruginosa (164); (ii) meropenem is not as potent as imipenem or doripenem against Acinetobacter baumannii (164);
Antipseudomonal carbapenems – imipenem, meropenem and doripenem – have excellent activity against most strains of many bacterial species and are regarded as safe and generally well-tolerated. Of note, these carbapenems are resistant to ESBLs, and so are of value in treating infections caused by ESBL-producing strains of Enterobacteriaceae
Source
unique application of meropenem is that when combined with clavulanic acid, it is potent at killing MDR Mycobacterium tuberculosis, a bacterium that typically is not susceptible to β-lactams due to a chromosomally expressed β-lactamase.
**Many class A β-lactamases are susceptible to inhibition by clavulanic acid (26). In contrast, all class C and most class D β-lactamases are not inhibited by clavulanic acid. However, class A and C and certain class D enzymes are inhibited by carbapenems. **
Several carbapenems were designed to target MRSA while maintaining activity against most Gram-negatives. The anti-MRSA activity is related to the high affinity of these compounds for PBP2a of MRSA. However, research on these compounds have been mostly abandoned. (Except for two)
Macrolides - Erythromycin has a very similar (not identical) spectrum to penicillin.
Mechanism: Macrolides inhibit the 50s ribosomal subunit and inhibit protein synthesis.
They are mainly bacteriostatic.
BUT both oral and IV erythromycin have significant side effects - so clarithromycin is used (having less SE but similar specturm. )
[!TIP] ==Penicillin ≈ clarithromycin==
So amoxicllin and clarithromycin are combined probably because they have different modes of action (although they have similar spectrums)
Clarithorymycin is good for
is a macrolide.
[!INFO] Gentamicin
Aminoglycoside antibiotic for gram -ve coverage.
Consider when penicillins are contraindicated and in mixed infections. Source
RE management of febrile neuropenia:
Give empirical antibiotics as per local policy and sensitivities:
• Commonly used antibiotics should include activity against enteric
Gram-negative bacteria and Pseudomonas, e.g. ceftazidime or
piperacillin–tazobactam with gentamicin; or meropenem monotherapy
Enterobacter, pseudomonas and Acinetobacter require high dose gentamicin / amikacin treatment.
Mechanism
Inhibition of protein synthesis by intefefering with ribosomal function.
Good activity against gram negatives - E. coli, klebsiella, psuedomonas,
Synegistic with penicillins used in endocarditis against Enterococcus and streptococcus viridans.
Amikacin - similar spectrum and has activity against gentamicin resistant organisms; only use if gentamicin won't work.
#2022SBR Q12
Gentamicin is supposed to cause ?non-oliguric renal failure!
No need for combination with metronidazole because it has good anaerobic coverage
Fluoroquinolone: Inhibits DNA synthesis.
Active against Streptococci, Staph epidermidis and some MRSA and also most gram -ve organisms including pseudomonas.
Works for acinetobacter! (Surprise!!)
A lincosamide - not a macrolide.
Inhibits protein formation by inhibiting the 50s ribosome.
Strongly assosiacted with C. difficile infection. Therefore, use should be minimized.
Doesn't penetrate the BBB -> can't use in meningitis.
Peak concentration reached within 60 minutes of oral administration.
Spectrum: Useful against gram +ve cocci --> severe streptococcal or staphylococcal cellulitis.
Has activity against PVL producing S. aureus.
A very high proportion of GI microbes are anaerobic.
Vancomycin or Teicoplanin.
Teicoplanin is a glycopeptide antibiotic that is almost identical to vancomycin with regard to its antibacterial spectrum of activity. - ScienceDirect
Teicoplanin is preferred in renal impairment.
#2022BSQ-MAY Q41
Microorganisms are
Obligate anaerobes are found as commensals in
Obligate anaerobes replicate at sites with low oxidation-reduction potential (eg, necrotic, devascularized tissue).
Anaerobic infections frequently occurs due to growth of a mixed population of bacteria with anerobes and facultative anaerobes.
Common sites of anaerobic infections:
Common gram negative anaerobic pathogens:
Common gram positive anaerobic infections:
Most of the pathogens we know are facultative anaerobic.
Obligate anaerobes include the following:
Anaerobic infections are usually suppurative.
Clues to suspect anaerobic infection:
Source
Antibiotics which are always active against anaerobes:
Aminoglycosides are not effective for anaerobes.
Vancomycin is active against Gram +ve anaerobes - (i.e clostridia)
Clindamycin - variable activity against anearobes. 40% of bacteroides and some clostridia are resistant.
Beta lactamases inactivate antibiotics with a beta-lactam ring.
Carbapenems are a sub-class of beta lactam antibiotics. Enzymes which inactivate carbapenems are called carbapenemases.
There are several types of microbial enzymes having beta lactamse activity; they have been c lassified by Ambler class.
Klebsiella pneumoniae carbapenemases (KPCs) are similar to ESBLs except that they also hydrolyze carbapenems!.
Beta lactamase inhibitors:
[!INFO] Development of cephalosporins
In 1945, after penicillin had been introduced into medicine, an antibiotic-producing species of Cephalosporium was isolated from a sewage outfall in Sardinia. Four years later in Oxford, this organism was found to produce several antibiotics, one of which was a penicillin with a new side-chain, penicillin N. During a chemical study in 1953, this penicillin was shown to be contaminated with a second substance, cephalosporin C, which contained a beta-lactam ring but was resistant to hydrolysis by a penicillinase (beta-lactamase). At that time, penicillinase-producing Staphylococci were causing a serious problem in hospitals. The isolation of the nucleus of cephalosporin C (7-ACA) enabled pharmaceutical manufacturers to produce many thousands of cephalosporins, some of which have been effective in the treatment of serious infections by a number of Gram-positive and Gram-negative bacteria.
Mechanism of action: They are beta lactam antibiotics; Mechanism of action: inhibition of bacterial cell wall synthesis
https://www.medigraphic.com/pdfs/lamicro/mi-2007/mi07-3_4g.pdf
First generation : most gram +ve cocci and some gram negative bacteria
(including penicillinase-producing Staphylococcus aureus)
"minimal coverage of gram -ves" but a few Gram -ves are susceptible.
(gram -ve's including E coli, klebsiella, proteus).
Clinically used for uncomplicated skin and soft tissue infections.
Cefuroxime
Haemophilus infeluenza, Moraxella, bacteroides
cefuroxime has increased coverage against H. influenzae.
Second-generation cephalosporins have less activity against gram-positive cocci than first-generation cephalosporins but have increased activity against gram-negative bacilli
They are often prescribed to treat respiratory infections such as bronchiolitis or pneumonia.
In addition to the gram-negative bacteria covered by first-generation cephalosporins, second-generation cephalosporins also have coverage against H. influenzae, Enterobacter aerogenes, Neisseria species, and Serratia marcescens
Less coverage against gram +ves but increased coverage Enterobacteriaceai, Neisseria and H influenzae.
Ceftazidime:
similar to gen 3 but better activity against gram -ves with antimicrobial resistance. (like beta lactamases)
Cefepime:
have coverage against MRSA and penicillin resistant pneumococci.
https://www.msdmanuals.com/professional/infectious-diseases/gram-negative-bacilli/haemophilus-infections
Fastidious gram -ve cocco-bacillus.
bacteremia, meningitis, pneumonia, sinusitis, otitis media, cellulitis, and epiglottitis
the most common is H. influenzae, which has 6 distinct encapsulated serotypes (a through f) and numerous nonencapsulated, nontypeable strains. Before the use of H. influenzae type b (Hib) conjugate vaccine, most cases of serious, invasive disease were caused by type b.
Non typable strains can cause upto half of H influenze infections in adults.
#2021BSQ-NOV Q18
[!WARNING] Most common HAI
It's a frequent cause of nosocomial infections; the most common pathogen isolated from patients hospitalized for > 1 week.
Going by the stuff that's already in this note:
#2020BSQ-NOV/Q19
Pseudomonas is a
#TODO
C. difficile
?"Power" - the probability of rejecting the null hypothesis when it is false.
#2021SBR-NOV/Q60
$$
Case; Fatality ;Ratio = \frac{Number;who;die}{Number;Diagnosed}
$$
Used for acute diseases.
the "proportion of those who become ill after a specified exposure over a specified time period"
Or
The "proportion of exposed people who become ill".
#2023SBR-NOV/Q09
OP is absorbed via skin, GI tract and respiratory tract!
Organphosphate inhibits acetylcholinesterase irreversibly, resulting in saturation of receptors with acetylcholine at
Acetylcholine is secreted by [[2020-BasicSciences-July#Autonomic nervous system and organization|several types of nerve endings.]]
Flooding with ACh causes the following symptoms.
[!INFO] OP poisoning symptoms
SLUDGE/BBB – Salivation, Lacrimation, Urination, Defecation, Gastric Emesis, Bronchorrhea, Bronchospasm, Bradycardia
At times, however, mydriasis and tachycardia may be observed, as sympathetic ganglia also contain nicotinic receptors